CCR6+ T helper cells and regulatory T cells in the blood and gastric mucosa during Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori (H. pylori) can evade the host's immune response and persist for a long time on the gastric mucosa. T helper (Th) cells appear to be involved in the control of H. pylori bacteria but promote mucosal inflammation. In contrast, regulatory T cells (Tregs) may reduce inflammation but promote H. pylori persistence. CC motif chemokine receptor 6 (CCR6) is involved in the migration of various cells into inflamed gastric mucosa. In this study, we examined CCR6+ Th cells and CCR6+ Tregs during H. pylori infection in humans. MATERIALS AND METHODS: Isolation of cells from blood and mucosal biopsies, magnetic separation of В cells, CD4+ and CD4+CCR6+CD45RO+ T cells, antigen-specific activation, B cell response in vitro, flow cytometry, determination of CD4+CD25hiFoxP3+ Tregs and various groups of Th cells. RESULTS: CD4+CCR6+ blood lymphocytes from healthy donors included Th cells and Tregs. These CCR6+ Th cells produced proinflammatory cytokines and also stimulated plasma cell maturation and antibody production in vitro. H. pylori gastritis and peptic ulcer disease were associated with an increase in the number of circulate CD4+CCR6+CD45RO+ cells and the percentage of Th1, Th17 and Th1/17 cells in this lymphocyte subgroup. In H. pylori-positive patients, circulating CD4+CCR6+ cells contained a higher proportion of H. pylori-specific cells compared with their CD4+CCR6- counterparts. H. pylori infection strongly increased the content of CD4+ lymphocytes in the inflamed gastric mucosa, with the majority of these CD4+ lymphocytes expressing CCR6. CD4+CCR6+ lymphocytes from H. pylori-infected stomach included Tregs and in vivo activated T cells, some of which produced interferon-γ without ex vivo stimulation. CONCLUSION: H. pylori infection causes an increase in the number of mature CD4+CCR6+ lymphocytes in the blood, with a pro-inflammatory shift in their composition and enrichment of the gastric mucosa with CD4+CCR6+ lymphocytes, including CCR6+ Th1 cells and Tregs.

Low-dose influenza vaccine Grippol Quadrivalent with adjuvant Polyoxidonium induces a T helper-2 mediated humoral immune response and increases NK cell activity.

The influenza vaccine Grippol® Quadrivalent (GQ) is a new vaccine, containing the adjuvant Polyoxidonium® and recombinant hemagglutinins from 4 strains of the influenza virus in amount of 5-6 µg of each hemagglutinin per human dose. These doses of antigens are about 3 times less than the standard dose recommended by WHO. We sought to characterize the immune response to the GQ vaccine and to determine the contribution of the adjuvant in this response. BALB/c mice were vaccinated with GQ or with adjuvant-free antigen mixtures (AGs). Then, the antibody response, the number of memory T cells in the spleen, and the functional properties of splenocytes were determined. The vaccine GQ has been shown to induce antibodies to all 4 influenza hemagglutinins. The vaccination with GQ caused a strong increase in the AG-induced proliferation and production of Th2 cytokines ex vivo. These effects were equal to effect achieved by standard dose of antigens. Vaccination also caused the accumulation of CD4+ large lymphocytes with the phenotype of central and effector memory T cells in the spleen. The GQ vaccine enhanced the cytolytic activity of natural killer (NK) cells, whereas the adjuvant-free mixture of AGs in lowered and standard doses did not affect NK activity. We did not find a noticeable response of Th1 and CD8+ T cells to vaccination. In vitro, the GQ vaccine stimulated the maturation of human monocyte-derived dendritic cells (DCs) enhancing the expression of HLA-DR, CD80, CD83, CD86 and ICOSL molecules. Polyoxidonium without AGs also induced expression of ICOSL, which plays an important role in T-dependent humoral immune response. In summary, the low-dose influenza vaccine GQ with Polyoxidonium adjuvant is immunogenic, induces a Th2-polarized T-cell response and CD4+ memory T cells maturation, activates the production of antibodies to influenza hemagglutinins, and increases the activity of NK cells.

Effect of cytotrophoblast cells on T lymphocyte surface antigen expression in cultures of peripheral blood mononuclear cells from pregnant woman and umbilical cord blood mononuclear cells from newborns.

We studied the action of cytotrophoblast cells (CTC) on the expression of T lymphocyte membrane markers in the cultures of newborn cord blood mononuclear cells (CBMC) and peripheral blood mononuclear cells (PBMC) of a pregnant woman. The CTC were separated from the placental chorion at ten weeks of gestation time. In this abstract we show that the CTC and the CTC culture supernatant (SN) increase the number of HLA DR(+)CD7(+) T cells activated by anti-CD3 mAbs, both in PBMC and CBMC cultures. CTC increased the number of transferrine receptor CD71(+) lymphocytes without anti-CD3 activation in CBMC cultures. The increase in the blood mononuclear cell proliferation did not come with an increase of HLA DR and CD71 expression induced by CTC or SN. Moreover, SN caused the suppression of activated T lymphocyte proliferation. We found no signs of any influence of CTC and SN on the expression of CD25 in CD4(+) and CD8(+) subpopulations of T lymphocytes, either activated or non-activated by anti-CD3. The data regarding the CTC- and SN-induced HLA DR expression in vitro suggest that the previously determined high level of HLA DR(+) T cells in the placenta and decidua in pregnant women might have been the result the activity of the trophoblast cells and their soluble products on the lymphocytes of that area.

The Cord Blood T cell Proliferation and Apoptosis: Influence of Interleukin-2, -4, -7 and Dexametasone.

We have shown that the severity of newborns' clinical condition is accompanied by two independent deviations in functional properties of T cells: week proliferative response to activation through CD3 molecule and high sensitivity to apoptosis. Studies of effects exerted by recombinant interleukins and dexamethasone upon cord blood mononuclear cell (CBMC) apoptosis proves that the IL-2, -4 and -7 deficiency is common to enhance apoptosis in CBMC cultures of newborn infants. However, interleukin deficiency is not the sole cause of high level of CBMC apoptosis, and some other factors are required, which may determine the cell sensitivity towards apoptosis. The weakness of proliferative response of T cells to activation seems to be determined rather by the effect of suppressive factors, production of which can be blocked by dexamethasone, than by the death of activated cells in apoptosis.